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A story of courage and risk-taking, House on Fire tells how smallpox, a disease that killed, blinded, and scarred millions over centuries of human history, was completely eradicated in a spectacular triumph of medicine and public health. Part autobiography, part mystery, the story is told by a man who was one of the architects of a radical vaccination scheme that became a key strategy in ending the horrible disease when it was finally contained in India. In House on Fire, William H. Foege describes his own experiences in public health and details the remarkable program that involved people from countries around the world in pursuit of a single objective--eliminating smallpox forever. Rich with the details of everyday life, as well as a few adventures, House on Fire gives an intimate sense of what it is like to work on the ground in some of the world's most impoverished countries--and tells what it is like to contribute to programs that really do change the world.

The global vaccination programme against smallpox led to its successful eradication and averted millions of deaths. Monkeypox virus (MPXV) is a close relative of the Variola (smallpox) virus. Due to antigenic similarity, smallpox vaccines cross-protect against MPXV. However, over 70% of people living today were never vaccinated against smallpox. Symptoms of monkeypox (MPX) include fever, head- and muscle ache, lymphadenopathy and a characteristic rash that develops into papules, vesicles and pustules which eventually scab over and heal. MPX is less often fatal (case fatality rates range from <1% to up to 11%) than smallpox (up to 30%). MPXV is endemic in sub-Saharan Africa, infecting wild animals and causing zoonotic outbreaks. Exotic animal trade and international travel, combined with the increasing susceptibility of the human population due to halted vaccination, facilitated the spread of MPXV to new areas. The ongoing outbreak, with >10,000 cases in >50 countries between May and July 2022, shows that MPXV can significantly spread between people and may thus become a serious threat to public health with global consequences. Here, we summarize the current knowledge about this re-emerging virus, discuss available strategies to limit its spread and pathogenicity and evaluate its risk to the human population.

Monkeypox is an emerging infectious disease for which outbreak frequency and expected outbreak size in human populations have steadily increased.1 The geographic spread of monkeypox cases has expanded beyond the forests of central Africa, where cases were initially found, to other parts of the world, where cases have been imported. This transmission pattern is likely due to the worldwide decline in orthopoxvirus immunity, following cessation of smallpox vaccination, once smallpox was declared eradicated in 1980. Monkeypox could therefore emerge as the most important orthopoxvirus infection in humans.2 We use mathematical modelling to argue that, in a population with diminishing herd immunity against orthopoxvirus species, the epidemic potential of monkeypox will continue increasing. Monkeypox is caused by the monkeypox virus, member of the orthopoxvirus genus in the Poxviridae family. This genus includes three other human pathogens: variola virus (causing smallpox), cowpox virus and vaccinia virus. Monkeypox and smallpox yield similar clinical presentations, with monkeypox causing lymphadenopathy, as a distinguishing feature, early in the disease course.2 Smallpox infection leads to long-lasting immunity; repeat attack rates of smallpox are just about 1 in 1000 for 15–20 years.3 Smallpox vaccination with vaccinia, a first-generation vaccine, also yields long-lasting immunity, with an efficacy of 80–95%. The current recommendation for revaccination is every 10 years, although longitudinal studies suggest that protection may last much longer.4 Vaccinia is also known to deliver long-lasting immunity against monkeypox, with 85% efficacy.5 Furthermore, studies of antibody responses to orthopoxvirus species suggest perfect cross-immunity between smallpox and monkeypox.

Background: Mpox is a disease endemic to Central and West Africa. It caused outbreaks in non-endemic countries, mainly in 2022. The endemic Democratic Republic of Congo is currently experiencing its largest outbreak yet. The vaccine Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) is approved for active immunization against mpox and smallpox. Since the outbreak in 2022, real-world studies have assessed MVA-BN's vaccine effectiveness (VE) against mpox, and this systematic literature review aims to summarize the most current evidence. Methods: Medline (via PubMed), Embase, and LILACS were searched, as well as grey literature sources and publications' bibliographies to identify observational studies published between 1/Jan/2022 and 28/Feb/2024 that estimate the VE of MVA-BN against mpox or provide risk measures that allow calculation of these VE estimates. Data were presented descriptively in tables and text; the methodological quality of included records was assessed using NHLBI/NIH quality assessment tools. Results: The literature search identified 16 records that fit the inclusion criteria. The studies took place in high-income countries and were heterogeneous in design, setting, and definition of at-risk populations. MVA-BN VE estimates against mpox infection were assessed. Where the study population was exclusively or primarily those receiving pre-exposure prophylactic vaccination, the adjusted VE estimates ranged from 35 % to 86 % (n = 8 studies) for one dose and from 66 % to 90 % (n = 5) for two doses. Where only post-exposure prophylactic vaccination was assessed, adjusted VE estimates were reported for one dose only at 78 % and 89 % (n = 2). Additionally, MVA-BN reduced the risk of mpox-related hospitalization in one study and the severity of mpox clinical manifestations in two studies. Conclusions: Despite heterogeneity in study design, setting, and at-risk populations, the reported VE estimates against mpox infection demonstrated the effectiveness of one or two doses of MVA-BN in the context of an outbreak across multiple countries. •We reviewed real-world evidence on the vaccine effectiveness of MVA-BN against mpox•Eligible studies were heterogeneous in design, setting, and at-risk populations•MVA-BN vaccination reduced the risk of mpox infections and hospitalization•MVA-BN vaccination reduced the severity of mpox clinical manifestations•Real-world evidence supports the use of MVA-BN for mpox outbreak control

More than four decades after the eradication of smallpox, the ongoing 2022 monkeypox outbreak and increasing transmission events of other orthopoxviruses necessitate a greater understanding of the global distribution of susceptibility to orthopoxviruses. We aimed to characterise the current global landscape of smallpox vaccination history and orthopoxvirus susceptibility. We characterised the global landscape of smallpox vaccination at a subnational scale by integrating data on current demography with historical smallpox vaccination programme features (coverage and cessation dates) from eradication documents and published literature. We analysed this landscape to identify the factors that were most associated with geographical heterogeneity in current vaccination coverage. We considered how smallpox vaccination history might translate into age-specific susceptibility profiles for orthopoxviruses under different vaccination effectiveness scenarios. We found substantial global spatial heterogeneity in the landscape of smallpox vaccination, with vaccination coverage estimated to range from 7% to 60% within admin-1 regions (ie, regions one administrative level below country) globally, with negligible uncertainty (99·6% of regions have an SD less than 5%). We identified that geographical variation in vaccination coverage was driven mostly by differences in subnational demography. Additionally, we found that susceptibility for orthopoxviruses was highly age specific based on age at cessation and age-specific coverage; however, the age profile was consistent across vaccine effectiveness values. The legacy of smallpox eradication can be observed in the current landscape of smallpox vaccine protection. The strength and longevity of smallpox vaccination campaigns globally, combined with current demographic heterogeneity, have shaped the epidemiological landscape today, revealing substantial geographical variation in orthopoxvirus susceptibility. This study alerts public health decision makers to non-endemic regions that might be at greatest risk in the case of widespread and sustained transmission in the 2022 monkeypox outbreak and highlights the importance of demography and fine-scale spatial dynamics in predicting future public health risks from orthopoxviruses. US National Institutes of Health and US National Science Foundation.

Monkeypox is caused by a pox virus closely related to smallpox virus and spreads from animals to humans, and humans to humans following close contact. Prior smallpox vaccination gives partial protection against monkeypox. The steady increase in monkeypox cases in Africa over the past few decades were ignored by the global scientific community till this year, when more than 16,000 cases have been reported from nonendemic countries. Monkeypox has recently been labelled as a public health emergency of international concern by the WHO. While most of the current cases are in men who have sex with men, there is the larger threat of the disease spilling into the general population. The disease is characterized by a short febrile illness with lymphadenopathy followed by a rash which spreads centrifugally and passes through phases of macules, papules, vesicles, and pustules. Recovery occurs in most patients within 2–4 wk. Complications are more likely in children, pregnant women, and the immunocompromised. Specific diagnosis is by detection of viral DNA by PCR. Treatment is largely symptomatic. Tecorivimat is a promising antiviral drug. Vaccination with the currently available smallpox vaccines is recommended for high-risk groups, health care workers, and close contacts. Control of the monkeypox outbreak needs a multipronged effort comprising enhanced surveillance, quick diagnosis, isolation of affected people, ring immunization, and adoption of “one health” approach.

Smallpox was declared to be eradicated on 8 May 1980, during the Thirty-third World Health Assembly. However, concerns about the possible use of the virus as a weapon of bioterrorism have increased in recent years. Governments have responded by initiating selective vaccination programmes and other public health measures. This review uses historical data from 20th century outbreaks to assess the risks to current populations (which have declining immunity) from a deliberate release of virus. The data presented supports the conclusion of a previous reviewer (Mack) that \"smallpox cannot be said to live up to its reputation. Far from being a quick-footed menace, it has appeared as a plodding nuisance with more bark than bite.\" Its R value (the average number of secondary cases infected by a primary case) is lower than that for measles, human parvovirus, chickenpox, mumps, rubella, and poliomyelitis; only the value for severe acute respiratory syndrome (SARS) is lower. Like SARS, close person-to-person contact is required for effective spread of the disease, and exposure to the virus in hospitals has played an important role in transmission for both viruses. In the present paper the dangers of mass vaccination are emphasized, along with the importance of case isolation, contact tracing, and quarantine of close contacts for outbreak control. The need for rapid diagnosis and the continued importance of maintaining a network of electron microscopes for this purpose are also highlighted.

Mpox (formerly known as monkeypox) is a zoonotic viral disease endemic in parts of Africa. In May, 2022, the world was alerted to circulation of monkeypox virus in many high-income countries outside of Africa. Continued spread resulted in a WHO declaration of a Public Health Emergency of International Concern. Although there has been much attention on the global outbreak, most of the focus has been on high-income countries outside of Africa, despite the fact that monkeypox virus has been causing disease in parts of Africa for at least 50 years. Furthermore, the long-term consequences of this event, especially the risk that mpox fills the niche vacated through smallpox eradication, have not been sufficiently considered. The heart of the problem is the historical neglect of mpox in Africa where the disease is endemic, and the actual and potential consequences if this neglect is left uncorrected.

In the annals of public health, smallpox is a watershed, being the first disease eradicated by vaccination. Drawing parallels to contemporary pandemic control measures, we examined the first smallpox vaccination campaigns in early 19th-century northern Italy and the seminal work of Luigi Sacco. Our study delves into this under-explored historical landscape to elucidate lessons that resonate with modern public health dilemmas. We scrutinised primary sources from the Historical Civic Archive of Pavia, the State Archive of Pavia, and the State Archive of Milan. These archives provided exhaustive data on administrative decrees, local epidemiology, and university-health authority collaborations. Using period-specific keyword searches and expert consultations, we extensively reviewed correspondence, vaccination lists, and academic writings, including Luigi Sacco's seminal Trattato di vaccinazione. The epidemiological investigation focused on the pivotal period of 1816–1828 in Lombardy's 19th-century public health landscape. Organisational reforms enacted in 1821 succeeded in doubling the number of vaccinations administered in Pavia, stabilising at elevated rates in subsequent years. Despite improvements, incongruities in epidemiological data and vaccinator remuneration persisted. Communication strategies pioneered by Sacco, encompassing academic and religious collaborations, demonstrated their efficacy. Epidemiological data revealed an initial surge in vaccination uptake in 1822, with a declining trend in the following years, notably impacted by logistical and data recording limitations. Our research underscores three salient dimensions pertinent to contemporary public health paradigms: first, the vital function of local administrative bodies as efficacious service providers, immunisation register keepers, and social safety nets; second, the equilibrium between mandatory vaccination policies and discretionary enforcement as a pragmatic framework for public compliance; lastly, the irrefutable importance of credible communication strategies in fighting vaccine hesitancy. These insights are not merely historical curiosities but cardinal principles for effectively managing modern epidemics and infectious disease threats. •Luigi Sacco was a pioneer in European smallpox vaccination in early 1800s Lombardy.•Historical analysis reveals similarities in vaccine campaign challenges then and now.•Local district organisation was the key to early widespread vaccine coverage.•Epidemiological data collection was a cornerstone for vaccination success.•Modern communication approaches and flexible mandates were crucial historically.

Reports of mpox are rising in Africa where the disease is endemic and in new countries where the disease has not been previously seen. The 2022 global outbreak of clade II mpox and an ongoing outbreak of the more lethal clade I mpox highlight the pandemic potential for monkeypox virus. Waning population immunity after the cessation of routine immunization for smallpox plays a key role in the changing epidemiologic patterns of mpox. Sustained human-to-human transmission of mpox is occurring widely in the context of insufficient population immunity, fueling genetic mutations that affect the accuracy of some diagnostic tests and that could lead to changing virulence. Additional research should address complex challenges for control of mpox, including improved diagnostics and medical countermeasures. The availability of vaccines should be expanded not only for outbreak response but also for broader routine use for persons in mpox-endemic countries.